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Biomedical subjects

J Lacour

Publications and source records attributed to J Lacour.

At least 19 recordsLinked to original sources

Polyadenylic-polyuridylic acid as an adjuvant in resectable colorectal carcinoma: a 6 1/2 year follow-up analysis of a multicentric double blind randomized trial.

In a double blind study, patients with operable carcinoma of the colon and the upper rectum, who have undergone a macroscopically complete resection of their tumor, were randomized to receive either (i) polyadenylic-polyuridylic acid (AU), one i.v. injection of 60 mg (in 50 ml of solution) once a week for 6 weeks, or (ii) a placebo (P) one i.v. injection of 50 ml of a saline solution with the same schedule. From January 1983 to December 1986, 288 patients were enrolled: 145 in AU group and 143 in P group. The main clinical and pathological characteristics were equally distributed throughout the two groups. There was a significant difference (P < 0.02) in the overall survival (OS) between the two groups, in favor of the P group. The 5-year OS rate was 68% (SD = 4%) in the AU group versus 81% (SD = 3%) in the P group. Thus, AU as a single adjuvant, appears to be ineffective and therefore has no indication in the treatment of colorectal carcinoma.

Aged

Polyadenylic-polyuridylic acid plus locoregional and pelvic radiotherapy versus chemotherapy with CMF as adjuvants in operable breast cancer. A 6 1/2 year follow-up analysis of a randomized trial of the French Federation of Cancer Centers (F.F.C.C.).

In this study, patients with operable breast cancer T2 or T3, treated by mastectomy + axillary dissection and with invaded axillary nodes (N+), were randomized to receive either: 1) postoperative locoregional and pelvic radiotherapy (RX) and Poly(A).Poly(U) (AU), 60 mg IV once a week for 6 weeks, or 2) CMF (cyclophosphamide 100 mg/sqm P.O. on days 1-14, methotrexate 40 mg/sqm IV on day 1 and 8, fluorouracil 600 mg/sqm IV on day 1 and 8; monthly cycle, for 6 months. Between March 1982 and December 1985, 517 patients were enrolled, 257 of whom were treated by RX + AU and 260 with CMF. The main clinical, pathological and prognostic characteristics were equally distributed in the two groups. The present analysis was conducted after a mean follow-up of 69 months (S.D. = 13). There was no significant difference in overall survival (OS) between the two groups (test adjusted by center and menopausal status); the five-year OS rate was 74% in the RXAU group and 77% in the CMF group. Relapse-free survival (RFS) was significantly higher (p = 0.05) in the RXAU group compared to the MCF group; the five-year RFS rates were 57% and 46% in the two groups respectively. This short, well-tolerated combined RXAU treatment appears to be as efficient as CMF and might offer an alternative to chemo- or hormonotherapy, in case of contraindications to these treatments.

Adult

Can internal mammary chain treatment decrease the risk of death for patients with medial breast cancers and positive axillary lymph nodes?

The effect of internal mammary chain treatment on each type of malignant death-related event was analyzed in 1195 patients with operable breast cancer and histologically involved axillary lymph nodes. A group of 135 patients who had no internal mammary chain treatment was compared with a control group of 1060 patients who were treated by surgery and/or postoperative radiation therapy. In a multivariate analysis taking into account age, clinical size of the tumor, histoprognostic grading, and the number of positive axillary lymph nodes, quantitative interaction tests were used to determine whether the effects of internal mammary chain treatment on each type of malignant event were significantly different for patients with a lateral tumor compared with those with a medial tumor. The authors found that the effects of this treatment on the risks of distant metastases and of secondary breast cancer were not the same for the patients with a medial tumor as for those with a lateral tumor. For the untreated patients with a medial tumor, the risks of distant metastases and second breast cancer were, respectively, 1.6 (P = 0.02) and 2.9 (P = 0.02), compared with the treated patients. Conversely, for women with lateral tumor, no difference between the two treatment groups was observed. Thus, internal mammary chain treatment may improve long-term survival rate in patients with a medial tumor and positive axillary lymph nodes essentially by decreasing the risk of development of distant metastases (mainly brain, distant lymph nodes, multiple simultaneous metastases) and/or a secondary breast cancer.

Adenocarcinoma

Ten-year results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer.

A randomized trial was conducted at the Institut Gustave-Roussy (IGR) between 1972 and 1980 comparing tumorectomy and breast irradiation with modified radical mastectomy. One hundred and seventy-nine patients with an infiltrating breast carcinoma up to 20 mm in diameter at macroscopic examination were included: 88 had conservative management, and 91 a mastectomy. All patients had a low-axillary dissection with immediate histological examination. For the patients with positive axillary nodes, a complete axillary dissection was undertaken. Overall survival, distant metastasis, contralateral breast cancer and locoregional recurrence rates were not significantly different between the two treatment groups.

Adenocarcinoma

Long-term effect of internal mammary chain treatment. Results of a multivariate analysis of 1195 patients with operable breast cancer and positive axillary nodes.

A multivariate analysis on 1195 patients with operable breast cancer and histologically positive axillary nodes treated by mastectomy and complete axillary dissection at the Institut Gustave-Roussy between 1958 and 1978 suggests a beneficial effect of treatment of the internal mammary chain (IMC) on the risks of death and distant metastasis for the patients with medial tumors. For these patients, surgical IMC dissection and post-operative irradiation have similar effects on both the risk of death and of distant metastasis. For the patients with lateral tumors, no beneficial effect of the treatment of the IMC on these two risks was observed. Postoperative irradiation to the IMC, axilla, chest wall and supraclavicular nodes significantly decreases the risk of locoregional recurrences independent of the tumor site and surgical management of the lymph nodes.

Adult

Polyadenylic-polyuridylic acid as adjuvant in the treatment of operable breast cancer: recent results.

A randomized trial of polyadenylic-polyuridylic acid (Poly(A).Poly(U) given as an adjuvant in the treatment of operable breast cancer, has included 300 patients of the Institut Gustave-Roussy from September 1972 to December 1979; 145 patients were allocated to conventional treatment alone and 155 to conventional treatment plus Poly(A).Poly(U). Reviews after mean periods of follow-up of 50 and 87 months were previously published. The present review performed after a mean follow-up period of 111 months confirmed a significant increase in the overall survival of patients with invaded nodes treated with Poly(A).Poly(U). The best results were achieved in the subset of patients with up to three affected nodes who showed a significant increase of both overall and relapse-free survival. The benefit seemed to be greater in postmenopausal women (P = 0.07). Present status of other ongoing trials of adjuvant Poly(A).Poly(U) is presented.

Breast Neoplasms

Is it useful to remove internal mammary nodes in operable breast cancer?

From September 1963 to January 1968, 243 patients with operable breast cancer were included in a randomized trial designed to compare classical radical mastectomy (RM) alone to extended mastectomy (EM), i.e. RM plus internal mammary dissection. One hundred and seventeen patients underwent RM, and 126 EM. After a mean follow-up time of 20 years, no significant differences were observed between the two treatment groups for overall survival, for the relapse-free survival rates, nor for distant metastasis, or locoregional recurrence rates. From a regression model, significant interactions were found between risk of death, EM, and both nodal status and site of the tumour. When compared to RM, EM significantly decreased the risk of death for patients with internal or medial tumour and positive axillary nodes (P = 0.05). No beneficial effect of EM was observed for any of the other patients; on the contrary, EM seemed to increase the risk of death for the patients with external tumour and negative axillary nodes (P = 0.07).

Breast Neoplasms

Enhancement of natural killer cell activity and 2-5A synthetase in operable breast cancer patients treated with polyadenylic; polyuridylic acid.

Treatment of operable breast cancer patients with a single injection of 60 mg poly(A); poly(U) (polyadenylic, polyuridylic acid) resulted in an enhancement of natural killer (NK) cell cytotoxicity against human myeloid K562 target cells. Furthermore, the level of 2-5A synthetase in peripheral blood lymphocytes of such patients was increased after the treatment. Both of these effects, measured 24 and 48 hours after the injection of poly(A); poly(U), were statistically significant compared to their respective levels before the treatment. These events, therefore, may be used as markers to monitor the immediate response of patients toward treatment with this synthetic double-stranded RNA.

2',5'-Oligoadenylate Synthetase

Polyadenylic.polyuridylic acid in the cotreatment of cancer.

The biological properties of polyadenylic . polyuridylic acid (Poly(A) . Poly(U] are discussed and the application to the treatment of cancer in various animal models is described. Pharmacokinetic properties are presented and the results of clinical application to humans with specific reference to adjuvant treatment of breast cancer are examined in some detail. Given these results and the total lack of toxicity or of secondary effects of Poly(A) . Poly(U) it appears that further development and application of this polynucleotide complex are certainly justified in terms of clinical use in cancer and perhaps in viral pathologies.

2',5'-Oligoadenylate Synthetase

Clinical trials using polyadenylic-polyuridylic acid as an adjuvant to surgery in treating different human tumors.

The results of a randomized trial of polyadenylic-polyuridylic [poly(A).poly(U)] acid given as adjuvant treatment for operable breast cancer were reviewed after a mean follow-up period of 87 months. The overall survival was significantly improved in patients given the adjuvant (155 cases) as compared with the controls (145 cases). A significant benefit was observed in patients with invaded axillary nodes; the best results were obtained in the group of patients with up to three nodes involved, who showed a significant increase in both overall and relapse-free survival. The biological response modifications observed after treatment with poly(A).poly(U), namely, production of interferon and increase of natural killer cell activity, are described and their possible role in the mechanism of action of the complex is discussed. The results of a Phase I clinical tolerance study of the duplex in cancer patients will be reported. The aims and protocols of new clinical trials with adjuvant poly(A).poly(U) in different types of tumors will be presented.

Breast Neoplasms

Conservative treatment versus mastectomy in breast cancer tumors with macroscopic diameter of 20 millimeters or less. The experience of the Institut Gustave-Roussy.

A clinical trial was conducted at the Institut Gustave Roussy between October 1972 and December 1980 to compare mastectomy with local excision plus Cobalt-irradiation, in patients with breast cancer tumors of 20 mm in diameter or less at macroscopic examination. Low-axillary dissection and extemporaneous histologic examination were carried out for all patients. If one or more positive nodes were found, complete axillary dissection was performed. The study included 179 patients. No significant difference was detected in either overall or relapse-free survival between the two groups, although the conservatively treated group showed slightly better results. The results of conservative treatment were esthetically satisfactory in 92% of the cases. The trial included a second randomization for the patients with positive axillary nodes to assess the value of nodal area irradiation; 72 patients were studied in this part of the trial. No significant differences were found between the two groups after adjustment for the number of positive axillary nodes, although the no-nodal irradiation group showed better results and less complications than the nodal irradiation group.

Axilla

Adjuvant treatment with polyadenylic-polyuridylic acid in operable breast cancer: updated results of a randomised trial.

The results of a randomised trial of polyadenylic-polyuridylic acid given as adjuvant treatment for operable breast cancer were reviewed after a mean follow up period of 87 months. Of the 300 patients included in the original trial, 145 had been allocated to conventional treatment alone and served as controls. At the time of review the overall survival of the group given polyadenylic-polyuridylic acid was significantly improved (p less than 0.05) as compared with that of the controls given conventional treatment alone. Significant benefit (p less than 0.02) was also observed among patients with evidence of disease in lymph nodes, the best results occurring in those with up to three invaded nodes, who showed a significant increase in both overall and relapse free survival. No evidence of toxicity was recorded. These findings confirm the value of polyadenylic-polyuridylic acid as adjuvant treatment for operable breast cancer. Results in an experimental model and in patients receiving the adjuvant suggested a possible role of interferon and natural killer (NK) cells in the mechanism of action.

Breast Neoplasms